Indian Journal of Private Psychiatry

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VOLUME 11 , ISSUE 2 ( July-December, 2017 ) > List of Articles

REVIEW ARTICLE

Use of Pupillometry in Dementia: A Review of Published Literature

Preeti Gupta, Shrikant Srivastava

Citation Information : Gupta P, Srivastava S. Use of Pupillometry in Dementia: A Review of Published Literature. Ind J Priv Psychiatry 2017; 11 (2):26-31.

DOI: 10.5005/jp-journals-10067-0006

License: CC BY-ND 3.0

Published Online: 00-12-2017

Copyright Statement:  Copyright © 2017; Jaypee Brothers Medical Publishers (P) Ltd.


Abstract

Introduction: Diagnosis of Alzheimer\'s disease is based on clinical symptomatology supplemented with neuroimaging findings. While there are invasive techniques like lumbar puncture and expensive techniques like positron emission tomography/ single photon emission computed tomography (PET)/SPECT imaging available for diagnosis, none of these are totally accurate. Thus, there is a need for a cheap and noninvasive technique for diagnosing Alzheimer\'s dementia. Pupillary light reaction or pupillometry is one such technique based on the hypothesis that the pupillary size and reaction are governed by the cholinergic system of the brain, which is deficient in Alzheimer\'s dementia. A review of the studies showed that pupillary measures have been studied in patients with or without mydriatic/miotic agents and in those receiving anticholinergic esterase medications. These studies are discussed in detail in this review.


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  1. Qiu C, De Ronchi D, Fratiglioni L. The epidemiology of the dementias: an update. Curr Opin Psychiatry 2007 Jul;20(4):380-385.
  2. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005 Dec;366(9503):2112-2117.
  3. Kihara T, Shimohama S. Alzheimer's disease and acetylcholine receptors. Acta Neurobiol Exp (Wars) 2004 Jan;64(1):99-106.
  4. Raskind MA, Peskind ER, Wessel T, Yuan W. Galantamine in AD: a 6-month randomized placebo controlled trial with a 6-month extension. Neurology 2000 Jun;54(12):2261-2268.
  5. Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT. A 24-week, double blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Neurology 1998 Jan;50(1):136-145.
  6. Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976 Dec; 308(8000):1403.
  7. Bowen DM, Smith CB, White PA, Davison AN. Neurotransmitter- related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 1976 Sep;99(3):459-496.
  8. Loewenfeld, IE. The pupil: anatomy, physiology and clinical applications. Vol. 1. Chapter 3. Boston (MA): Butterworth- Heinemann; 1991.
  9. Hunter S. The rostral mesencephalon in Parkinson's disease and Alzheimer's disease. Acta Neuropathol 1985 Mar;68(1):53-58.
  10. Scinto LF, Wu CK, Firla KM, Daffner KR, Saroff D, Geula C. Focal pathology in the Edinger-Westphal nucleus explains pupillary hypersensitivity in Alzheimer's disease. Acta Neuropathol 1999 May;97(6):557-564.
  11. Bittner DM, Wieseler I, Wilhelm H, Riepe MW, Muller NG. Repetitive pupil light reflex: potential marker in Alzheimer's disease? J Alzheimers Dis 2014 Jan;42(4):1469-1477.
  12. Fotiou DF, Stergiou V, Tsiptsios D, Lithari C, Nakou M, Karlovasitou A. Cholinergic deficiency in Alzheimer's and Parkinson's disease: evaluation with pupillometry. Int J Psychophysiol 2009 Aug;73(2):143-149.
  13. Fotiou DF, Brozou CG, Haidich AB, Tsiptsios D, Nakou M, Kabitsi A, Giantselidis C, Fotiou F. Pupil reaction to light in Alzheimer's disease: evaluation of pupil size changes and mobility. Aging Clin Exp Res 2007 Oct;19(5):364-371.
  14. Granholm E, Morris S, Galasko D, Shults C, Rogers E, Vukov B. Tropicamide effects on pupil size and pupillary light reflexes in Alzheimer's and Parkinson's disease. Int J Psychophysiol 2003 Feb;47(2):95-115.
  15. Tales A, Troscianko T, Lush D, Haworth J, Wilcock GK, Butler SR. The pupillary light reflex in aging and Alzheimer's disease. Aging (Milano) 2001 Dec;13(6):473-478.
  16. Takagi A, Miyao M, Ishihara SY, Sakakibara H, Kondo T, Toyoshima H, Kono K, Iguchi A. Sensitive pupil response of early-onset Alzheimer's patients to a dilute mixture of cholinergic antagonist and ƒ¿-Adrenergic stimulant. Environ Health Prev Med 1999 Apr;4(1):49-53.
  17. Sacks B, Smith S. People with Down's syndrome can be distinguished on the basis of cholinergic dysfunction. J Neurol Neurosurg Psychiatry 1989 Nov;52(11):1294-1295.
  18. Kono K, Miyao M, Ishihara S, Takagi A, Ikari H, Suzuki Y, Iguchi A. Hypersensitivity in the pupil dilation response to a cholinergic antagonist in patients with Alzheimer's disease and Down's syndrome. Nihon Ronen Igakkai Zasshi 1996 Nov;33(11):829-834.
  19. Iijima A, Haida M, Ishikawa N, Ueno A, Minamitani H, Shinohara Y. Re-evaluation of tropicamide in the pupillary response test for Alzheimer's disease. Neurobiol Aging 2003 Oct;24(6):789-796.
  20. Treloar AJ. 1995
  21. Hanyu H, Hirao K, Shimizu S, Kanetaka H, Sakurai H, Iwamoto T. Phenylephrine and pilocarpine eye drop test for dementia with Lewy bodies and Alzheimer's disease. Neurosci Lett 2007 Mar;414(2):174-177.
  22. Giza E, Fotiou D, Bostantjopoulou S, Katsarou Z, Karlovasitou A. Pupil light reflex in Parkinson's disease: evaluation with pupillometry. Int J Neurosci 2011 Jan;121(1):37-43.
  23. Stergiou V, Fotiou D, Tsiptsios D, Haidich B, Nakou M, Giantselidis C, Karlovasitou A. Pupillometric findings in patients with Parkinson's disease and cognitive disorder. Int J Psychophysiol 2009 May;72(2):97-101.
  24. Frost S, Kanagasingam Y, Sohrabi H, Bourgeat P, Villemagne V, Rowe CC, Macaulay LS, Szoeke C, Ellis KA, Ames D, et al. Pupil response biomarkers for early detection and monitoring of Alzheimer's disease. Curr Alzheimer Res 2013 Nov;10(9):931-939.
  25. Kaneyuki H, Mitsuno S, Nishida T, Yamada M. Enhanced miotic response to topical dilute pilocarpine in patients with Alzheimer's disease. Neurology 1998 Mar;50(3):802-804.
  26. Katz B. Detecting Alzheimer's disease [letter]. Science 1995 Mar;267(5204):1578-1581.
  27. Pomara N, Sitaram N. Detecting Alzheimer's disease [letter]. Science 1995 Mar;267(5204):1579-1580.
  28. Scinto LF, Daffner KR, Dressler D, Ransil BI, Rentz D, Weintraub S, Mesulam M, Potter H. A potential noninvasive neurobiological test for Alzheimer's disease. Science 1994 Nov;266(5187):1051-1054.
  29. Grunberger J, Linzmayer L, Walter H, Rainer M, Masching A, Pezawas L, Saletu-Zyhlarz G, Stohr H, Grunberger M. Receptor test (pupillary dilatation after application of 0.01% tropicamide solution) and determination of central nervous activation (Fourier analysis of pupillary oscillations) in patients with Alzheimer's disease. Neuropsychobiology 1999 Jul;40(1):40-46.
  30. Higuchi S, Matsushita S, Hasegawa Y, Muramatsu T, Arai H. Pupillary response to tropicamide in Japanese patients with alcoholic dementia, Alzheimer's disease, and vascular dementia. Exp Neurol 1997a Mar;144(1):199-201.
  31. Higuchi S, Matsushita S, Hasegawa Y, Muramatsu T, Arai H, Hayashida M. Apolipoprotein E ɛ4 allele and pupillary response to tropicamide. Am J Psychiatry 1997 May;154(5): 694-696.
  32. Kálmán J, Kanka A, Maglóczky E, Szóke A, Járdánházy T, Janka Z. Increased mydriatic response to tropicamide is a sign of cholinergic hypersensitivity but not specific to late-onset sporadic type of Alzheimer's dementia. Biol Psychiatry 1997 Apr;41(8):909-911.
  33. Arai H, Terajima M, Nakagawa T, Higuchi S, Mochizuki H, Sasaki H. Pupil dilatation assay by tropicamide is modulated by apolipoprotein E e4 allele dosage in Alzheimer's disease. Neuroreport 1996 Mar;7(4):918-920.
  34. Gómez-Tortosa E, del Barrio A, Jiménez-Alfaro I. Pupil response to tropicamide in Alzheimer's disease and other neurodegenerative disorders. Acta Neurol Scand 1996 Aug;94(2):104-109.
  35. Imamura Y, Kojima H, Haraoka K. Pupil dilation response to the acetylcholine receptor antagonist tropicamide in normal aged and senile dementia subjects. Neurobiol Aging 1996 Dec;17(4):S165.
  36. Woodruff-Pak DS, Romano SJ, Hinchliffe RU. Detection of Alzheimer's disease with eye blink classical conditioning and the pupil dilation response. Alzheimers Res 1996 Jan;2: 173-180.
  37. Mahmoudian M, Ebrahimi SA, Kiani Z. An image processing technique for diagnosis of Alzheimer's disease. J Res Med Sci 2009 Jul;14(4):205-209.
  38. Scinto LF. Pupillary cholinergic hypersensitivity predicts cognitive decline in community dwelling elders. Neurobiol Aging 2008 Feb;29(2):222-230.
  39. Kardon RH. Drop the Alzheimer's drop test. Neurology 1998 Mar;50(3):588-591.
  40. Ferrario E, Molaschi M, Villa L, Varetto O, Bogetto C, Nuzzi R. Is videopupillography useful in the diagnosis of Alzheimer's disease? Neurology 1998 Mar;50(3):642-644.
  41. Fotiou F, Fountoulakis KN, Tsolaki M, Goulas A, Palikaras A. Changes in pupil reaction to light in Alzheimer's disease patients: a preliminary report. Int J Psychophysiol 2000 Jul;37(1):111-120.
  42. Caputo L, Casartelli M, Perrone C, Santori M, Annoni G, Vergani C. The ‘eye test’ in recognition of late-onset Alzheimer's disease. Arch Gerontol Geriatr 1998 Oct;27(2):171-177.
  43. Fitz-Simon JS, Waring SC, Kokmen E, McLaren JW, Brubaker RF. Response of the pupil to tropicamide is not a reliable test for Alzheimer disease. Arch Neurol 1997 Feb;54(2):155-159.
  44. Fridh M, Havelius U, Elofsson G, Hindfelt B. The pupillary response to tropicamide in Alzheimer's disease. Acta Ophthalmol Scand 1996 Jun;74(3):276.279.
  45. Graff-Radford NR, Lin SC, Brazis PW, Bolling JP, Liesegang TJ, Lucas JA, Uitti RJ, O'Brien PC. Tropicamide eyedrops cannot be used for reliable diagnosis of Alzheimer's disease. Mayo Clin Proc 1997 Jun;72(6):495-504.
  46. Growdon JH, Graefe K, Tennis M, Hayden D, Schoenfeld D, Wray SH. Pupil dilation to tropicamide is not specific for Alzheimer disease. Arch Neurol 1997 Jul;54(7):841-844.
  47. Kurz A, Marquard R, Fremke S, Leipert KP. Pupil dilation response to tropicamide: a biological test for Alzheimer's disease? Pharmacopsychiatry 1997 Jan;30(1):12-15.
  48. Loupe DN, Newman NJ, Green RC, Lynn MJ, Williams KK, Geis TC, Edelhauser HF. Pupillary response to tropicamide in patients with Alzheimer disease. Ophthalmology 1996 Mar;103(3):495-503.
  49. Marx JL, Kumar SR, Thach AB, Kiat-Winarko T, Frambach DA. Detecting Alzheimer's disease. Science 1995 Mar;267(5204):1577.
  50. Reitner A, Baumgartner I, Thuile C, Dilmaghani RB, Ergun E, Kaminski S, Lukas J, Dal Bianco P. Rapid communication the mydriatic effect of tropicamide and its diagnostic use in Alzheimer's disease. Vis Res 1997 Jan;37(1):165-168.
  51. Treloar AJ, Assin M, MacDonald AJ. Pupillary response to topical tropicamide as a marker for Alzheimer's disease. Br J Clin Pharmacol 1996 Mar;41(3):256-257.
  52. Robles A. Some remarks on biological markers of Alzheimer's disease. Neurobiol Aging 1998 Apr;19(2):153-157.
  53. Grünberger J, Linzmayer L, Walter H, Stohr H, Saletu- Zyhlarz GM, Grunberger M, Lesch OM. Psychophysiological diagnostics in alcohol dependency: Fourier analysis of pupillary oscillations and the receptor test for determination of cholinergic deficiency. Alcohol Alcohol 1998 Sep-Oct; 33(5):541-548.
  54. Litvan I, FitzGibbon EJ. Can tropicamide eye drop response differentiate patients with progressive supranuclear palsy and Alzheimer's disease from healthy control subjects? Neurology 1996 Nov;47(5):1324-1326.
  55. Harris JP. The pupil in Parkinson's disease. J Psychophysiol 1991;5(3):251-254.
  56. Micieli G, Tassorelli C, Martignoni E, Pacchetti C, Bruggi P, Magri M, Nappi G. Disordered pupil reactivity in Parkinson's disease. Clin Auton Res 1991 Mar;1(1):55-58.
  57. Beaumont SM, Harris JP, Leendertz JA, Phillipson OT. The pupillary light reflex in mild Parkinsons-disease. Clin Vis Sci 1987 Jan;2(2):123-129.
  58. Matsushita S, Arai H, Hasegawa Y, Tcrajima M, Muramatsu T, Sasaki H, Higuchi S. 754 Apolipoprotein E ε4 allele and pupillary response to tropicamide in Alzheimer's disease and cognitively normal subjects. Neurobiol Aging 1996 Dec;17 (4 Suppl 1):S187.
  59. Hasegawa S, Ishikawa S. Age changes in pupillary light reflex. A demonstration by means of a pupillometer. Nippon Ganka Gakkai Zasshi 1989 Oct;93(10):955-961.
  60. Lowenstein O, Loewenfeld IE. The sleep-waking cycle and pupillary activity. Ann N Y Acad Sci 1964 Sep;117(1):142-156.
  61. Jacobson and Olson 1993.
  62. Drummond. 1991.
  63. Prettyman R, Bitsios P, Szabadi E. Altered pupillary size and darkness and light reflexes in Alzheimer's disease. J Neurol Neurosurg Psychiatry 1997 Jun;62(6):665-668.
  64. Fitz-Simon JS, et al. 1997.
  65. Katz et al., 1988.
  66. Sitaram N, Pomara P. Increased pupillary miotic response to pilocarpine in cognitively impaired elderly subjects. IRCS Med Sci 1981 Jan;9:409-410.
  67. Canver, MC.; Canver, AC.; Revere, KE.; Amado, D.; Bennett, J.; Chung, DC. Algorithm for pupillometric data analysis. In: Bioengineering Conference, Proceedings of the 2010 IEEE 36th Annual Northeast. New York (NY): IEEE; 2010. p. 1-2.
  68. Tsorlinis H, Goulas A, Alexopoulos L, Fotiou F, Fountoulakis K, Tsolaki M. 412 changes in the pupil reaction to light in Alzheimer's disease patients. Int J Psychophysiol 1998 Sep;30(1):159-160.
  69. Hardy J. Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci 1997 Apr;20(4):154-159.
  70. Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K, et al. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 1995 Aug;269(5226):973-977.
  71. Mayer Gross, W.; Slater, E.; Roth, M. Clinical psychiatry. 3rd ed. London: Baillier, Tindall & Carssell; 1969.
  72. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 2013 Jan;9(1):63.e2-75.e2.
  73. Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T, et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 1995 Aug;376(6543):775-778.
  74. Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 1995 Jun;375(6534):754-760.
  75. Cole PA, Robinson CH. Mechanism and inhibition of cytochrome P-450 aromatase. J Med Chem 1990;33:2933-42.
  76. Akhtar M, Njar VC, Wright JN. Mechanistic studies on aromatase and related C-C bond cleaving P-450 enzymes. J Steroid Biochem Mol Biol 1993;44:375-87.
  77. Palter SF, Tavares AB, Hourvitz A, Veldhuis JD, Adashi EY. Are estrogens of import to primate/human ovarian folliculogenesis? Endocr Rev 2001;22:389-424.
  78. Weil S, Vendola K, Zhou J, Bondy CA. Androgen and follicle stimulating hormone interactions in primate ovarian follicle development. J Clin Endocrinol Metab 1999;84:2951-56.
  79. Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest 1998;101:2622-29.
  80. Giudice LC. Insulin-like growth factors and ovarian follicular development. Endocr Rev 1992;13:641-69.
  81. Mitwally MF, Casper RF. Aromatase inhibitors for the treatment of infertility. Expert Opin Investig Drugs 2003;12:353-71.
  82. Mitwally MF, Biljan MM, Casper RF. Pregnancy outcome after the use of an aromatase inhibitor for ovarian stimulation. Am J Obstet Gynecol 2005;192:381-86.
  83. Mitwally MFM, Casper RF. The use of aromatase inhibitor for induction of ovulation in cases of clomiphene citrate failure. Curr Opin Obstet Gynecol 2002;14:255-63.
  84. Mitwally MF, Casper RF. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril 2001;75:305-09.
  85. Sammour A, Bijan MM, Tan SL, Tulandi T. Prospective randomised trial comparing the effects of letrazole (LE) and clomiphene citrate (CC) on follicular development, endometrial thickness and pregnancy rate in patients undergoing superovulation prior to intrauterine insemination (IUI). Fertil Steril 2001;76(Suppl 1):S110.
  86. Mitwally MF, Casper RF. Single-dose administration of an aromatase inhibitor for ovarian stimulation. Fertil Steril 2005;83:229-31.
  87. Fisher SA, Reid RL, Van Vugt DA, Casper RF. A randomized double-blind comparison of the effects of clomiphene citrate and the aromatase inhibitor letrozole on ovulatory function in normal women. Fertil Steril 2002;78:280-85.
  88. Fatemi HM, Kalibianakis E, Tournaye H, Camus M, Van Steirteghem AC, Devroey P. Clomiphene citrate vs letrozole for ovarian stimulation: A pilot study. Reprod Biomed Online 2003;7:543-46.
  89. Hu Y, Cortvrindt R, Smitz J. Effects of aromatase inhibition on in vitro follicle and oocyte development analyzed by early preantral mouse follicle culture. Mol Reprod Dev 2002;61: 549-59.
  90. Shetty G, Krishnamurthy H, Krishnamurthy HN, Bhatnagar S, Moudgal NR. Effect of estrogen deprivation on the reproductive physiology of male and female primates. J Steroid Biochem Mol Biol 1997;61:157-66.
  91. Mitwally MF, Casper RF. Aromatase inhibition reduces gonadotrophin dose required for controlled ovarian stimulation in women with unexplained infertility. Hum Reprod 2003;18:1588-97.
  92. Mitwally MF, Casper RF. Aromatase inhibition improves ovarian response to follicle-stimulating hormone in poor responders. Fertil Steril 2002;77:776-80.
  93. Goswami SK, Das T, Chattopadhyay R, Sawhney V, Kumar J, Chaudhury K, Chakravarty BN, Kabir SN. A randomized single blind controlled trial of letrozole as a low-cost IVF protocol in women with poor ovarian response: A preliminary report. Hum Reprod 2004;19:2031-35.
  94. Newkirk KM, Chandler HL, Parent AE, et al. Ultraviolet radiation-induced corneal degeneration in 129 mice. Toxicol Pathol 2007;35:819-26.
  95. Pettenati MJ, Sweatt AJ, Lantz P, et al. The human cornea has a high incidence of acquired chromosome abnormalities. Hum Genet 1997;101:26-29.
  96. Snibson GR. Collagen cross-linking: A new treatment paradigm in corneal disease—a review. Clin Experiment Ophthalmol 2010;38:141-53.
  97. Spoerl E, Raiskup-Wolf F, Kuhlisch E, Pillunat LE. Cigarette smoking is negatively associated with keratoconus. J Refract Surg 2008;24:S737-40.
  98. Rabinowitz YS, Nesburn AB, McDonnell PJ. Videokeratography of the fellow eye in unilateral keratoconus. Ophthalmology 1993;100:181-86.
  99. Goodrich DW, Lee WH. The molecular genetics of retinoblastoma. Cancer Surv 1990;9:529-54.
  100. Moodaley LC, Woodward EG, Liu CS, Buckley RJ. Life expectancy in keratoconus. Br J Ophthalmol 1992;76:590-91.
  101. Honein MA, Dawson AL, Petersen EE, Jones AM, Lee EH, Yazdy MM, Ahmad N, Macdonald J, Evert N, Bingham A, et al. Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy. JAMA 2017 Jan 3;317(1):59-68.
  102. Chervenak FA, Jeanty P, Cantraine F, Chitkara U, Venus I, Berkowitz RL, Hobbins JC. The diagnosis of fetal microcephaly. Am J Obstet Gynecol 1984 Jul 1;149(5):512-517.
  103. Papageorghiou AT, Thilaganathan B, Bilardo CM, Ngu A, Malinger G, Herrera M, Salomon LJ, Riley LE, Copel JA. ISUOG Interim Guidance on ultrasound for Zika virus infection in pregnancy: information for healthcare professionals. Ultrasound Obstet Gynecol 2016 Apr;47(4):530-532.
  104. Chibueze EC, Parsons AJ, Lopes KD, Yo T, Swa T, Nagata C, Horita N, Morisaki N, Balogun OO, Dagvadorj A, et al. Diagnostic accuracy of ultrasound scanning for prenatal microcephaly in the context of Zika virus infection: a systematic review and meta-analysis. Sci Rep 2017 May 23;7(1):2310.
  105. Cordeiro MT. Zika virus: laboratory diagnosis. In: Zika in focus. Springer International Publishing; 2017. pp. 59-62.
  106. Mlakar J, Korva M, Tul N, Popović M, Poljšak-Prijatelj M, Mraz J, Kolenc M, Resman Rus K, Vesnaver Vipotnik T, Fabjan Vodušek V, et al. Zika virus associated with microcephaly. N Engl J Med 2016 Mar 10;374(10):951-958.
  107. Zare Mehrjardi M, Keshavarz E, Poretti A, Hazin AN. Neuroimaging findings of Zika virus infection: a review article. Jpn J Radiol 2016 Dec;34(12):765-770.
  108. Oliveira Melo AS, Malinger G, Ximenes R, Szejnfeld PO, Alves Sampaio S, Bispo de Filippis AM. Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol 2016 Jan;47(1):6-7.
  109. Araujo AQ, Silva MT, Araujo AP. Zika virus-associated neurological disorders: a review. Brain 2016;139(8):2122-2130.
  110. Brasil P, Pereira JP Jr, Moreira ME, Ribeiro Nogueira RM, Damasceno L, Wakimoto M, Rabello RS, Valderramos SG, Halai UA, Salles TS, et al. Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med 2016 Dec 15;375(24):2321-2334.
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